The role of the Chemistry Core during the lead optimization phase is to conduct a thorough exploration of the structural requirements necessary for maximal activity against each target. The topological orientation of the substituents defines the pharmacophore from which the biological activity is derived. Chemical modification of the functional groups and rings present in the lead molecules will be carried out to enhance activity and potency of the molecules. Regions of the molecules that are deemed not critical for activity may be modified to improve physicochemical properties such as aqueous solubility, lipophilicity, and chemical stability, as well as pharmacokinetic and toxicological properties (ADME/T) of the molecules. In addition, the Chemistry Core is responsible for developing formulation strategies for the lead molecules to optimize plasma exposure in animals and to develop methods to synthesize kilogram quantities of material for the IND-enabling toxicology studies required before proceeding into studies in humans.